What happens when you take oral contraceptives with folate?
A 2015 systematic review and meta-analysis published in the Journal of Obstetrics and Gynaecology Canada pooled data from observational studies comparing folate status in oral contraceptive users and non-users. It found a mean reduction of 1.27 micrograms per liter in plasma folate and 59.32 micrograms per liter in red blood cell folate among pill users. The mechanism is not fully settled but appears to involve increased urinary excretion of folate metabolites, altered enterohepatic recycling, and possibly changes in the intestinal absorption of folate from food.
The reduction is modest in healthy women with adequate dietary folate. For women with marginal intake, restricted diets, or genetic polymorphisms in folate metabolism (such as MTHFR C677T), the same percentage drop can push folate status into a range associated with reproductive risk.
Why is this important?
Folate's most critical role is in early neural tube closure, which happens between days 21 and 28 after conception, often before a woman knows she is pregnant. Inadequate folate during this window is the strongest modifiable risk factor for neural tube defects such as spina bifida and anencephaly. Public health guidance from the CDC and the U.S. Preventive Services Task Force recommends that all women of reproductive age consume 400 mcg of folic acid daily, regardless of whether they are actively trying to conceive.
For women coming off the pill, this matters because fertility can return immediately. A meaningful fraction of pregnancies are conceived within the first one to two months after stopping a combined pill. If folate stores are depleted at that moment, the window of vulnerability for the neural tube is exactly when intake matters most. That is why the FDA approved oral contraceptives containing levomefolate calcium (Beyaz in 2010 and Safyral in 2010) at 451 mcg per tablet, specifically to maintain folate status during pill use.
What should you do?
Maintain folate stores throughout your reproductive years if you are on the pill, even if pregnancy is not in your immediate plans.
- Take 400 mcg of folic acid or methylfolate daily, ideally through a multivitamin or prenatal vitamin. This is the same recommendation made for all women who could become pregnant.
- If you have an MTHFR variant or have been told you are a poor methylator, consider L-5-methyltetrahydrofolate (the active form) at the same dose.
- Consider a folate-containing oral contraceptive such as Beyaz or Safyral if you find a daily supplement hard to remember. Each tablet delivers 451 mcg of levomefolate calcium.
- If you plan to stop the pill to try to conceive, continue folate for at least three months before and throughout early pregnancy. Increase to 800 mcg if you have had a prior pregnancy with a neural tube defect or take antiseizure medications.
- Include folate-rich foods most days: leafy greens (spinach, romaine), legumes (lentils, black beans), citrus fruits, asparagus, broccoli, and fortified grains.
Which specific products are affected?
The depletion is documented for combined oral contraceptives containing ethinyl estradiol with progestins (Yaz, Yasmin, Lo Loestrin Fe, Ortho Tri-Cyclen, Sprintec, generic equivalents). Progestin-only pills have less data but appear to have a smaller effect. The patch and ring deliver ethinyl estradiol systemically and likely produce comparable changes.
For supplementation, you have several options. A standard multivitamin or prenatal usually contains 400 to 800 mcg of folate. Standalone folic acid tablets at 400 mcg are inexpensive and effective for most women. Methylfolate (5-MTHF, sometimes labeled as Quatrefolic or Metafolin) is preferred by women with MTHFR variants and is the form used in Beyaz and Safyral.
Folate-containing oral contraceptives Beyaz (drospirenone 3 mg / ethinyl estradiol 20 mcg / levomefolate calcium 451 mcg) and Safyral (drospirenone 3 mg / ethinyl estradiol 30 mcg / levomefolate calcium 451 mcg) deliver hormone and folate in one tablet, but they remain combined oral contraceptives and carry the same VTE and other risks as drospirenone-containing pills.
The bottom line
Oral contraceptives modestly lower folate status, and a non-trivial number of women conceive shortly after stopping the pill, when low folate is most consequential. Take 400 mcg of folate daily during your reproductive years if you use hormonal contraception, either through a multivitamin, a prenatal, or a folate-containing pill formulation. This is simple, cheap, and prevents a serious birth defect risk that does not announce itself in advance.